This program is dedicated to understanding the mechanisms of immune senescence. Five interrelated projects will be carried out. The first project investigates the mechanism of the age-associated impairment in human t lymphocyte proliferation. The role of shifts in the distribution of T cell subsets, the production of t cell growth factors and expression of growth factor receptors will be studied. The second project explores the role of thymic proteins as regulators of cell growth and differentiation. The third project explores the effect of age-associated thymic involution on intra-thymic positive and negative selection of T cells. The fourth project investigates the cellular and molecular basis for the age-associated increase in benign, serum monoclonal immunoglobulins. The fifth project examines the mechanisms underlying the defects in macrophage function that occur with age.